The Project (Homologous Recombination and Crosslink Repair) integrates into the SBDR Program[unreadable] Project by focusing upon the lesion removal step of the overall cellular response to DMA double[unreadable] strand breaks and interstrand crosslinks. Genetic studies have shown a pivotal role of homologous[unreadable] recombination in double-strand break and crosslink repair pathways. There is ample evidence that[unreadable] homologous recombination repair (HRR) and companion DNA damage signaling reactions are[unreadable] critical for genome maintenance. Deregulation of these biological pathways leads to several[unreadable] cancers and diseases predisposing to cancer, including familial breast and ovarian cancers[unreadable] (BRCA1 and BRCA2), Fanconi anemia (FANCD2 and BRCA2), and Ataxia telangiectasia (ATM).[unreadable] As with other DNA repair systems, HRR entails extensive protein-protein and protein-ligand[unreadable] interactions. Our research project strives to decipher the molecular basis of the hierarchy of[unreadable] interactions that modulate the efficiency of HRR and crosslink removal. To achieve our objectives,[unreadable] collaborative studies described under four Aims will be carried out. Specifically, we will (1)[unreadable] determine the molecular basis of the Rad52 recombination mediator activity needed for Rad51[unreadable] presynaptic filament assembly, (2) delineate the significance of the interactions of Rad51 with Pir51[unreadable] and also BRCA2 Exon 27, (3) examine the biochemical interaction between FANCD2 and ATM and[unreadable] define the role of FANCD2 in Rad51-mediated reactions, and (4) determine the basis for complex[unreadable] assemblies involving BARD1 and its partner proteins and define the influence of the BRCA1-[unreadable] BARD1 complex on the Rad51 recombinase activity.